What is the clinical evidence for common iron supplements and recommended dosing for different age/sex groups?
Executive summary
Clinical trials and systematic reviews show pregnancy-and-menstruation">oral iron reliably raises hemoglobin and iron stores in people with iron deficiency or iron-deficiency anemia, with clear public-health benefits for infants in high‑anemia settings and for menstruating women in high‑prevalence areas [1] [2] [3]. Recent physiologic research and randomized trials have refined how much elemental iron to give, which salt to choose, and whether daily versus alternate/weekly dosing optimizes absorption and tolerability [4] [5] [6].
1. What the clinical evidence shows about effectiveness
Randomized trials and cohort studies demonstrate that oral iron increases hemoglobin, ferritin and related markers and can improve symptoms such as fatigue and some cognitive measures in iron‑deficient people; for example, trials in non‑anemic fatigued adults and in blood donors showed measurable benefit after weeks of therapy [1] [6] [7]. Systematic reviews support daily iron as a public‑health intervention to prevent iron deficiency and anemia in infants 6–23 months in high‑prevalence settings and to reduce anemia and iron deficiency in menstruating women where anemia prevalence is high [2] [3] [8]. Evidence quality varies by outcome and population, but benefit for correcting deficiency and improving hematologic indices is consistent [7].
2. Which iron supplements are studied and how they compare
Most clinical trials use ferrous salts (ferrous sulfate, ferrous fumarate, ferrous gluconate) and carbonyl iron; products include tablets, capsules, syrups and combination preparations, with ferrous salts being the most commonly prescribed because of established efficacy [1]. Comparative evidence is limited but indicates standard ferrous salts effectively raise hemoglobin; newer low‑dose or proprietary formulations have shown benefit in trials of mild deficiency and fatigue, though head‑to‑head superiority is not well established [1]. Carbonyl iron at 45 mg daily reduced deficiency in blood donors in a randomized trial, showing alternatives to high‑dose ferrous sulfate can be effective [6].
3. Recommended dosing by age and sex from guidelines and trials
For infants 6–23 months in high‑anemia settings, WHO recommends universal supplementation of about 2 mg/kg/day when diets lack fortified foods or anemia prevalence exceeds 40% [9] [2]. For non‑pregnant menstruating women, WHO and Cochrane summaries support daily iron in high‑prevalence populations and an international recommendation exists for weekly intermittent supplements containing 60 mg elemental iron plus folic acid for non‑pregnant women of reproductive age where programmatic delivery is used [3] [5]. Randomized trials in adult women show benefit with daily doses as low as 45 mg carbonyl iron over 8 weeks [6]. Pregnancy increases iron needs and many guidelines use higher daily targets (the commonly quoted RDA during pregnancy is 27 mg elemental iron, noted in guideline summaries) but public‑health antenatal programs often use higher therapeutic doses for anemia [10] [2]. In the very elderly, randomized data indicate low doses (15–50 mg elemental iron daily) can be as effective as 150 mg with fewer adverse effects [11] [12].
4. Schedule matters: hepcidin biology and alternate‑day dosing
Physiologic studies measuring serum hepcidin and iron absorption show single oral doses ≥60 mg in iron‑deficient women (and ≥100 mg in frank IDA) raise hepcidin for ~24 hours, suppressing next‑day absorption; giving 60–120 mg as a morning single dose on alternate days increases fractional absorption and may reduce side effects compared with daily divided dosing [4]. These mechanistic data have led experts to recommend considering alternate‑day dosing for many non‑severe cases to optimize net iron uptake [4].
5. Safety, interactions and practical caveats
Gastrointestinal side effects (nausea, constipation, dark stools) are common and dose‑related; systematic reviews rate evidence for GI harms variably but note increased stool discoloration with supplementation [8]. Iron supplements can reduce absorption of drugs like levodopa and interact with calcium; vitamin C modestly increases absorption, but a randomized trial found adding vitamin C to iron did not change clinical outcomes compared with iron alone in established IDA [13] [9]. Upper tolerable intake limits and the need to investigate causes of anemia before long‑term therapy are emphasized in geriatric and clinical guidance [11].
6. Controversies, evidence gaps and practical takeaways
Open questions include optimal ferritin thresholds for treatment across sexes and ages (critically discussed in calls to revise ferritin reference ranges), the best public‑health schedule in mixed‑malaria settings, and long‑term comparative effectiveness of lower‑dose or alternate‑day regimens in diverse populations [14] [2] [4]. Clinically, use established ferrous salts for treatment of IDA, consider 45–100 mg elemental iron daily for women depending on severity with alternate‑day dosing increasingly supported for absorption and tolerability, follow WHO 2 mg/kg/day guidance for infants in high‑prevalence settings, and favor lower doses in the very elderly while investigating underlying causes [6] [4] [9] [11]. Reporting limitations: many recommendations derive from public‑health program data or physiologic studies rather than large head‑to‑head trials for every age/sex subgroup [2] [4].